Beyond Weight Loss: Novo and Lilly Look to Expand Their GLP-1 Pipelines

A spate of clinical trial results for Novo Nordisk and Eli Lilly’s GLP-1 receptor agonists in indications outside of obesity and diabetes highlight how both companies are looking to diversify the uses for these blockbuster drugs.

Last month Lilly released positive Phase III findings for tirzepatide, marketed for weight loss as Zepbound, in sleep apnea. It now plans to seek FDA approval for this indication.

Meanwhile, in March Novo received FDA approval for semaglutide, marketed for weight loss as Wegovy, to reduce cardiovascular death, heart attack and stroke in adults who have cardiovascular disease and are obese or overweight. That same month, the company released promising results from a Phase IIIb trial of semaglutide in kidney disease.

Lilly is also pursuing a GLP-1 option for kidney disease, and both companies have authorized studies for nonalcoholic steatohepatitis (NASH, or MASH). Novo is also testing GLP-1s for Alzheimer’s disease. These markets are undeniably smaller than that for weight-loss drugs, but the lure of GLP-1s’ ability to treat such wide-ranging diseases is nonetheless driving their expanding reach.

“I think weight loss will remain predominant,” James Shehan, chair of FDA Regulatory Practice at Lowenstein Sandler and former long-time counsel at Novo Nordisk, told BioSpace. “But I think you’re going to have more and more recognition that obesity is a complex panoply of conditions. And that by treating obesity, you address a whole lot of physical ills that people might have.”

Originally used to treat type 2 diabetes, GLP-1 receptor agonists rose to fame with their ability to help people lose weight. Indeed, GLP-1s have become the predominant drug class discussed for weight loss. In a February review article published in Nature about the future of obesity treatment, for example, the authors pointed exclusively to innovations in the GLP-1 space.

“GLP-1 is used as the backbone of obesity treatments because it has multiple positive effects,” co-author Dimitris Papamargaritis, associate professor of diabetes and endocrinology at the University of Leicester, told BioSpace. “By using this as backbone, we’re trying to combine some extra properties that the other molecules may bring.”
(Papamargaritis has previously received clinical trial grant funding from Novo Nordisk, as well as speaker fees from both Novo Nordisk and Eli Lilly.)

Despite the focus on diabetes and obesity, research suggests broad pharmacological potential for GLP-1s. A review from the National Institutes of Health documented that, in addition to the traditionally understood benefits of the hormone, this drug class “has cardio- and neuroprotective effects, decreases inflammation and apoptosis, and has implications for learning and memory, reward behavior, and palatability.”

Indeed, GLP-1 research has diversified to include non-alcoholic fatty liver disease, polycystic ovary syndrome, peripheral arterial disease and cardiovascular health, among others.

Lilly’s lead extension of its GLP-1 program is sleep apnea, with the recently released Phase III results showing the trial met all primary and key secondary endpoints. The company is also studying tirzepatide in MASH, with results of a Phase II clinical trial released in June showing the drug to be superior to placebo. The company’s novel triple agonist GLP-1, retatrutide, is also in Phase III clinical trials as a treatment for sleep apnea and knee osteoarthritis, in addition to obesity and T2D. Results are expected in 2026.

In the cardiovascular space, Lilly has conducted Phase III trials surveying the effect of tirzepatide on long-term risk for atherosclerotic cardiovascular disease (ASCVD) and on heart failure with preserved ejection fraction together with obesity. Results released in November 2023 for the former indication showed that the treatment significantly reduced the 10-year predicted risk of ASCVD, though the company has not stated plans to apply for an approval in this space. Results for the latter are anticipated this month.

For its part, Novo aims to build on its success in cardiovascular risk reduction earlier this year with plans to apply for regulatory approval for semaglutide in kidney disease in the U.S. and Europe in 2024, with the March results demonstrating a 24% reduction in the risk of kidney disease–related events. The company also has an ongoing Phase III trial concerning MASH, with a projected completion date of 2029.

Finally, Novo is running two concurrent Phase III clinical trials testing semaglutide in early Alzheimer’s; results from these studies are expected in late 2026. Interestingly, an observational study published in July found that patients with type 2 diabetes taking Novo’s Ozempic (semaglutide) had lower risks of dementia, cognitive deficit and nicotine misuse.

With Eli Lilly and Novo Nordisk both doubling down on their GLP-1 pipelines, it should be no surprise that a report from June 2024 estimated that the global GLP-1 market was worth an estimated $36.8 billion in 2023, with projected growth to $138 billion by 2031.

Notably, this report considered two applications for GLP-1s: type 2 diabetes and obesity. The new markets Novo and Lily are looking to enter are significantly smaller, but they nonetheless have the potential to supplement profits for GLP-1 treatments. Industry market reports project the Alzheimer’s market to grow from $4.8 billion to $8.18 billion by 2032 and MASH/NASH to grow from $1.62 to $24.2 billion by 2028.

“The demand for GLP-1 drugs will grow, and at a potentially substantial rate, if manufacturers obtain FDA-approval for treating nonalcoholic fatty liver disease, polycystic ovary syndrome, sleep apnea, diabetes prevention and other benefits without new serious adverse effects,” Patrick Gleason, assistant vice president for Health Outcomes at Prime Therapeutics and Magellan Rx, a pharmacy benefits management company, told BioSpace in an email.